Intervention fidelity in the definitive cluster randomised controlled trial of the Healthy Lifestyles Programme (HeLP) trial: findings from the process evaluation.

BACKGROUND: The Healthy Lifestyles Programme (HeLP) was a novel school-located intervention for 9-10 year olds, designed to prevent obesity by changing patterns of child behaviour through the creation of supportive school and home environments using dynamic and creative delivery methods. This paper reports on both the quantitative and qualitative data regarding the implementation of the HeLP intervention in the definitive cluster randomised controlled trial, which was part of the wider process evaluation. METHODS: Mixed methods were used to collect data on intervention uptake, fidelity of delivery in terms of content and quality of delivery of the intervention, as well as school and child engagement with the programme. Data were collected using registers of attendance, observations and checklists, field notes, focus groups with children and semi-structured interviews with teachers. Qualitative data were analysed thematically and quantitative data were summarized using descriptive statistics. RESULTS: All 16 intervention schools received a complete or near complete programme (94-100%), which was delivered in the spirit in which it had been designed. Of the 676 children in the intervention schools, over 90% of children participated in each phase of HeLP; 92% of children across the socio-economic spectrum were deemed to be engaged with HeLP and qualitative data revealed a high level of enjoyment by all children, particularly to the interactive drama workshops. Further evidence of child engagment with the programme was demonstrated by children's clear understanding of programme messages around marketing, moderation and food labelling. Thirteen of the intervention schools were deemed to be fully engaged with HeLP and qualitative data revealed a high level of teacher 'buy in', due to the programme's compatability with the National Curriculum, level of teacher support and use of innovative and creative delivery methods by external drama practitioners. CONCLUSION: Our trial shows that it is possible to successfully scale up complex school-based interventions, engage schools and children across the socio-economic spectrum and deliver an intervention as designed. As programme integrity was maintained throughout the HeLP trial, across all intervention schools, we can be confident that the trial findings are a true reflection of the effectiveness of the intervention, enabling policy recommendations to be made. TRIAL REGISTRATION: ISRCTN15811706

Fidelity and moderating factors in complex interventions: a case study of a continuum of care program for frail elderly people in health and social care

<p>Abstract</p> <p>Background</p> <p>Prior studies measuring fidelity of complex interventions have mainly evaluated adherence, and not taken factors affecting adherence into consideration. A need for studies that clarify the concept of fidelity and the function of factors moderating fidelity has been emphasized. The aim of the study was to systematically evaluate implementation fidelity and possible factors influencing fidelity of a complex care continuum intervention for frail elderly people.</p> <p>Methods</p> <p>The intervention was a systematization of the collaboration between a nurse with geriatric expertise situated at the emergency department, the hospital ward staff, and a multi-professional team with a case manager in the municipal care services for older people. Implementation was evaluated between September 2008 and May 2010 with observations of work practices, stakeholder interviews, and document analysis according to a modified version of The Conceptual Framework for Implementation Fidelity.</p> <p>Results</p> <p>A total of 16 of the 18 intervention components were to a great extent delivered as planned, while some new components were added to the model. No changes in the frequency or duration of the 18 components were observed, but the dose of the added components varied over time. Changes in fidelity were caused in a complex, interrelated fashion by all the moderating factors in the framework, i.e., context, staff and participant responsiveness, facilitation, recruitment, and complexity.</p> <p>Discussion</p> <p>The Conceptual Framework for Implementation Fidelity was empirically useful and included comprehensive measures of factors affecting fidelity. Future studies should focus on developing the framework with regard to how to investigate relationships between the moderating factors and fidelity over time.</p> <p>Trial registration</p> <p>ClinicalTrials.gov, <a href="http://www.clinicaltrials.gov/ct2/show/NCT01260493">NCT01260493</a>.</p

Implementing the LifeSkills Training drug prevention program: factors related to implementation fidelity

<p>Abstract</p> <p>Background</p> <p>Widespread replication of effective prevention programs is unlikely to affect the incidence of adolescent delinquency, violent crime, and substance use until the quality of implementation of these programs by community-based organizations can be assured.</p> <p>Methods</p> <p>This paper presents the results of a process evaluation employing qualitative and quantitative methods to assess the extent to which 432 schools in 105 sites implemented the LifeSkills Training (LST) drug prevention program with fidelity. Regression analysis was used to examine factors influencing four dimensions of fidelity: adherence, dosage, quality of delivery, and student responsiveness.</p> <p>Results</p> <p>Although most sites faced common barriers, such as finding room in the school schedule for the program, gaining full support from key participants (i.e., site coordinators, principals, and LST teachers), ensuring teacher participation in training workshops, and classroom management difficulties, most schools involved in the project implemented LST with very high levels of fidelity. Across sites, 86% of program objectives and activities required in the three-year curriculum were delivered to students. Moreover, teachers were observed using all four recommended teaching practices, and 71% of instructors taught all the required LST lessons. Multivariate analyses found that highly rated LST program characteristics and better student behavior were significantly related to a greater proportion of material taught by teachers (adherence). Instructors who rated the LST program characteristics as ideal were more likely to teach all lessons (dosage). Student behavior and use of interactive teaching techniques (quality of delivery) were positively related. No variables were related to student participation (student responsiveness).</p> <p>Conclusion</p> <p>Although difficult, high implementation fidelity by community-based organizations can be achieved. This study suggests some important factors that organizations should consider to ensure fidelity, such as selecting programs with features that minimize complexity while maximizing flexibility. Time constraints in the classroom should be considered when choosing a program. Student behavior also influences program delivery, so schools should train teachers in the use of classroom management skills. This project involved comprehensive program monitoring and technical assistance that likely facilitated the identification and resolution of problems and contributed to the overall high quality of implementation. Schools should recognize the importance of training and technical assistance to ensure quality program delivery.</p

Protein Phosphatase 2A Interacts with the Na+,K+-ATPase and Modulates Its Trafficking by Inhibition of Its Association with Arrestin

Background: The P-type ATPase family constitutes a collection of ion pumps that form phosphorylated intermediates during ion transport. One of the best known members of this family is the Na +,K +-ATPase. The catalytic subunit of the Na +,K +-ATPase includes several functional domains that determine its enzymatic and trafficking properties. Methodology/Principal Findings: Using the yeast two-hybrid system we found that protein phosphatase 2A (PP2A) catalytic C-subunit is a specific Na +,K +-ATPase interacting protein. PP-2A C-subunit interacted with the Na +,K +-ATPase, but not with the homologous sequences of the H +,K +-ATPase. We confirmed that the Na +,K +-ATPase interacts with a complex of A- and C-subunits in native rat kidney. Arrestins and G-protein coupled receptor kinases (GRKs) are important regulators of G-protein coupled receptor (GPCR) signaling, and they also regulate Na +,K +-ATPase trafficking through direct association. PP2A inhibits association between the Na +,K +-ATPase and arrestin, and diminishes the effect of arrestin on Na +,K +-ATPase trafficking. GRK phosphorylates the Na +,K +-ATPase and PP2A can at least partially reverse this phosphorylation. Conclusions/Significance: Taken together, these data demonstrate that the sodium pump belongs to a growing list of io

Choline transporter gene variation is associated with attention-deficit hyperactivity disorder

The neurotransmitter acetylcholine (ACh) plays a critical role in brain circuits mediating motor control, attention, learning and memory. Cholinergic dysfunction is associated with multiple brain disorders including Alzheimer’s Disease, addiction, schizophrenia and Attention-Deficit Hyperactivity Disorder (ADHD). The presynaptic choline transporter (CHT, SLC5A7) is the major, rate-limiting determinant of ACh production in the brain and periphery and is consequently upregulated during tasks that require sustained attention. Given the contribution of central cholinergic circuits to the control of movement and attention, we hypothesized that functional CHT gene variants might impact risk for ADHD. We performed a case-control study, followed by family-based association tests on a separate cohort, of two purportedly functional CHT polymorphisms (coding variant Ile89Val (rs1013940) and a genomic SNP 3’ of the CHT gene (rs333229), affording both a replication sample and opportunities to reduce potential population stratification biases. Initial genotyping of pediatric ADHD subjects for two purportedly functional CHT alleles revealed a 2–3 fold elevation of the Val89 allele (n = 100; P = 0.02) relative to healthy controls, as well as a significant decrease of the 3’SNP minor allele in Caucasian male subjects (n = 60; P = 0.004). In family based association tests, we found significant overtransmission of the Val89 variant to children with a Combined subtype diagnosis (OR = 3.16; P = 0.01), with an increased Odds Ratio for a haplotype comprising both minor alleles. These studies show evidence of cholinergic deficits in ADHD, particularly for subjects with the Combined subtype, and, if replicated, may encourage further consideration of cholinergic agonist therapy in the disorder

Modeling rare gene variation to gain insight into the oldest biomarker in autism: construction of the serotonin transporter Gly56Ala knock-in mouse

Alterations in peripheral and central indices of serotonin (5-hydroxytryptamine, 5-HT) production, storage and signaling have long been associated with autism. The 5-HT transporter gene (HTT, SERT, SLC6A4) has received considerable attention as a potential risk locus for autism-spectrum disorders, as well as disorders with overlapping symptoms, including obsessive-compulsive disorder (OCD). Here, we review our efforts to characterize rare, nonsynonymous polymorphisms in SERT derived from multiplex pedigrees carrying diagnoses of autism and OCD and present the initial stages of our effort to model one of these variants, Gly56Ala, in vivo. We generated a targeting vector to produce the Gly56Ala substitution in the Slc6a4 locus by homologous recombination. Following removal of a neomycin resistance selection cassette, animals exhibiting germline transmission of the Ala56 variant were bred to establish a breeding colony on a 129S6 background, suitable for initial evaluation of biochemical, physiological and behavioral alterations relative to SERT Gly56 (wildtype) animals. SERT Ala56 mice were achieved and exhibit a normal pattern of transmission. The initial growth and gross morphology of these animals is comparable to wildtype littermate controls. The SERT Ala56 variant can be propagated in 129S6 mice without apparent disruption of fertility and growth. We discuss both the opportunities and challenges that await the physiological/behavioral analysis of Gly56Ala transgenic mice, with particular reference to modeling autism-associated traits

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe